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INTRODUCTION: Penetrating neck trauma (PNT) due to gunshot injuries is one of the challenging conditions with the potential for both significant morbidities and mortality. RESEARCH QUESTION: There are significant concerns in the approach to patients with spinal gunshot injuries. Surgery indications, methods of surgery, and management of CSF leaks are the main concerns of these patients. METHODS AND MATERIALS: An 11-year-old boy was referred to our center with a single gunshot wound to the left side of the posterior cervical region 2 days ago with cerebrospinal fluid leakage and left arm weakness. RESULTS: The patient underwent surgery, and the pellet was removed. His left arm weakness fully recovered after the operation, and no new symptoms developed during the 1-year follow-up. CONCLUSION: Timely surgery could dramatically improve outcomes in PNT patients with mild symptoms and prevent worsening neurological defects.
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Vazamento de Líquido Cefalorraquidiano , Ferimentos por Arma de Fogo , Humanos , Masculino , Ferimentos por Arma de Fogo/cirurgia , Ferimentos por Arma de Fogo/complicações , Criança , Vazamento de Líquido Cefalorraquidiano/cirurgia , Vazamento de Líquido Cefalorraquidiano/etiologia , Paresia/etiologia , Paresia/cirurgia , Extremidade Superior/cirurgia , Extremidade Superior/lesões , Lesões do Pescoço/cirurgia , Lesões do Pescoço/complicaçõesRESUMO
PURPOSE: Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI. METHODS: Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data. RESULTS: 785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies). CONCLUSION: Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
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Fatores Inibidores da Migração de Macrófagos , Traumatismos da Medula Espinal , Animais , Estudos Transversais , Humanos , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológicoRESUMO
BACKGROUND: Breast cancer is the most prevalent malignancies among the women that have a high mortality. Previous studies demonstrated that hypericin, a bioactive component of Hypericum perforatum have a cytotoxic effect on the malignant cell lines. However, an anti-carcinogenic activity of hypericin on MCF-7 is uncertain. To investigate the cytotoxic effect of hypericin on MCF-7 cells, a human breast adenocarcinoma cell-line, that resistance to chemotherapy. METHODS: The MCF-7 and fibroblast (as normal cell line) were treated with various concentrations of hypericin, and Cisplatin as a positive control for 24 and 48 h. Cytotoxicity activity was measured and confirmed by MTT assay and Trypan blue staining, respectively. In addition, Apoptosis were determined by Annexin V/Propidium Iodide assay. Immunocytochemistry (ICC) analysis for bcl2 and p53 proteins performed to further investigate different expression of these genes in different samples. RESULTS: Both cisplatin and the hypericin exhibited a dose-dependent cytotoxic effect in the MCF-7 cell line. Although the LD50 of the hypericin was significantly lower when compared to cispaltin (5 vs. 20 µg/ml), it continued to decrease the growth rate of the MCF-7 cells when tested at higher concentration than LD50. In contrast, cisplatine, at higher concentration than LD50, completely inhibited the growth of the MCF-7 in 48 h. Regarding Annexin V/Propidium results, treatment of MCF-7 cells with LD50 concentration of cisplatin and hypericin showed 60 and 52 % apoptosis in 24 h, respectively. ICC analysis for bcl2 and p53 also confirmed our results; in treated samples for the dose of LD50 in 24 and 48 h of cisplatin and hypercin, more cells expressed p53 (guardian of cells in front of tumor formation/progression) and less expressed bcl2 (which has anti apoptotic activity) compared to untreated samples. CONCLUSIONS: Considering that hypericin showed to be cytotoxic, it seems to be a chemopreventive agent and a good candidate for antineoplastic drug development.
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BACKGROUND: Glioblastoma (GBM) is a malignant brain tumor that frequently occurs alongside other central nervous system (CNS) conditions. The secretome of GBM cells contains a diverse array of proteins released into the extracellular space, influencing the tumor microenvironment. These proteins can serve as potential biomarkers for GBM due to their involvement in key biological processes, exploring the secretome biomarkers in GBM research represents a cutting-edge strategy with significant potential for advancing diagnostic precision, treatment monitoring, and ultimately improving outcomes for patients with this challenging brain cancer. AIM: This study was aimed to investigate the roles of secretome biomarkers and their pathwayes in GBM through bioinformatics analysis. METHODS AND RESULTS: Using data from the Gene Expression Omnibus and the Cancer Genome Atlas datasets-where both healthy and cancerous samples were analyzed-we used a quantitative analytical framework to identify differentially expressed genes (DEGs) and cell signaling pathways that might be related to GBM. Then, we performed gene ontology studies and hub protein identifications to estimate the roles of these DEGs after finding disease-gene connection networks and signaling pathways. Using the GEPIA Proportional Hazard Model and the Kaplan-Meier estimator, we widened our analysis to identify the important genes that may play a role in both progression and the survival of patients with GBM. In total, 890 DEGs, including 475 and 415 upregulated and downregulated were identified, respectively. Our results revealed that SQLE, DHCR7, delta-1 phospholipase C (PLCD1), and MINPP1 genes are highly expressed, and the Enolase 2 (ENO2) and hexokinase-1 (HK1) genes are low expressions. CONCLUSION: Hence, our findings suggest novel mechanisms that affect the occurrence of GBM development, growth, and/or establishment and may also serve as secretory biomarkers for GBM prognosis and possible targets for therapy. So, continued research in this field may uncover new avenues for therapeutic interventions and contribute to the ongoing efforts to combat GBM effectively.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Glioblastoma , Células-Tronco Neoplásicas , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Secretoma/metabolismo , Perfilação da Expressão Gênica , Transdução de Sinais , Prognóstico , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Microambiente TumoralRESUMO
STUDY DESIGN: A systematic review and meta-analysis OBJECTIVE: To determine the global frequency of osteomyelitis in individuals with spinal cord injury who have pressure injuries (SCI-PI). METHODS: A comprehensive search on PubMed, EMBASE, Scopus, and the Web of Science has been conducted until November 2023. The Cochrane Handbook for Systematic Reviews was followed. Cohort and cross-sectional studies included SCI-PI participants who reported the frequency of osteomyelitis without language restriction. Data extraction was performed by four reviewers in two groups. We used the Newcastle-Ottawa Quality Assessment Scale for quality assessment. The Chi-squared and I2 tests were applied to detect heterogeneity between studies. Also, a random-effects model was performed for the report data. RESULTS: Ten out of 986 studies met our eligibility criteria, with 492 SCI-PI individuals. It was discovered that most SCIs were thoracolumbar injuries and male. There was a history of PI in more than half the patients. SCI was primarily caused by trauma. A meta-analysis revealed a significantly heterogeneous 43.0% osteomyelitis frequency. There was no evidence of publication bias. Subgroup analysis based on study quality revealed that the frequency of osteomyelitis in low-quality studies was 34.5%, whereas the frequency in high-quality research was 47.4%. Furthermore, the overall frequency of osteomyelitis was 29.0% in the subgroup analysis of research carried out in the USA. CONCLUSIONS: Our study highlights the significant burden of osteomyelitis among SCI-PI individuals. These findings underscore the pressing need for standardized diagnostic and management protocols to mitigate the morbidity associated with osteomyelitis in this vulnerable population.
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Osteomielite , Úlcera por Pressão , Traumatismos da Medula Espinal , Humanos , Osteomielite/epidemiologia , Osteomielite/etiologia , Úlcera por Pressão/epidemiologia , Úlcera por Pressão/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologiaRESUMO
BACKGROUND: Glioblastoma is associated with low median survival time irrespective of maximal treatment. Previous in vitro studies have revealed tumor inhibitory effect of cyclosporine A. However, whether the addition of cyclosporine could improve survival among patients with glioblastoma is unknown. This study aimed to determine the impact of postoperation treatment with cyclosporine on the survival and performance status. METHODS: In this randomized, triple-blinded, placebo-controlled trial, 118 patients with glioblastoma who underwent surgery were treated with standard chemoradiotherapy regimen. Patients were randomized to receive intravenous cyclosporine for 3 days postoperatively or placebo during the same period. The primary endpoint was the short-term effect of intravenous cyclosporine on survival and Karnofsky performance scores. Secondary endpoints were chemoradiotherapy toxicity and neuroimaging features. RESULTS: The overall survival (OS) in the cyclosporine (17.03 ± 5.8, 95% confidence interval: 11-17.37 months) group was statistically lower than in the placebo (30.53 ± 4.9, 95% confidence interval: 8-32.3 months) groups (P = 0.049). However, compared to the placebo group, a statistically higher percentage of patients in the cyclosporine group were alive at 12 months follow-up. Also, progression-free survival in the cyclosporine group was significantly prolonged than in the placebo group (6.3 ± 4.07 months vs. 3.4 ± 2.98 months, P < 0.001). In the multivariate analysis, age <50 years (P = 0.022) and gross total resection (P = 0.03) were significantly associated with OS. CONCLUSIONS: Our study results demonstrated that administering postoperative cyclosporine does not improve OS and functional performance status. Notably, the survival rate was significantly dependent on the patient age and the extent of glioblastoma resection.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Pessoa de Meia-Idade , Glioblastoma/tratamento farmacológico , Glioblastoma/cirurgia , Glioblastoma/patologia , Ciclosporina/uso terapêutico , Quimiorradioterapia/métodos , Avaliação de Estado de Karnofsky , Administração Intravenosa , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgiaRESUMO
Introduction: Breast cancer is the major leading cause of death from cancer among women. Given the drug resistance seen during the treatment of this disease, it is very important to identify new therapies and new anticancer drugs. Some studies indicate the cytotoxic effects of cyanidin 3-glycoside (C3G). Therefore, this study aims to evaluate the anticancer effect of C3G in the treatment of the MCF-7 cell line. Material and methods: In this study, the MCF-7 cell line was treated with different concentrations of C3G for 24 and 48 h. Assessment of cell death was performed by MTT assay. The cell apoptosis rate was measured using an Annexin V/propidium iodide assay through flow cytometry. The expression levels of p53, Bax, Caspase3, CYP1, CYP2, and Bcl2 genes were evaluated using polymerase chain reaction, and Western blotting was performed for CYP1 to confirm the results. Results: Our findings showed that C3G has dose-dependent cytotoxic effects on the MCF-7 cell line. According to flow cytometry results, the apoptosis of the cells 24 h after exposure to C3G was more than 51.5%. Moreover, after 24 h of exposure to the half-maximal inhibitory concentration of C3G, the expression of p53, Bax, Caspase3, CYP1, and CYP2 genes increased, and the expression of Bcl2 gene decreased. The Western blotting showed that CYP1 protein increased 2-fold compared to the control sample. Conclusions: The results of this study demonstrated that C3G has apoptotic and cytotoxic effects on breast cancer cells. Therefore, it is likely that this substance could be a suitable option for cancer therapy.
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BACKGROUND: Atorvastatin is a member of statins, which has shown positive vascular effects, anti-oxidant, anti-platelet, and anti-apoptotic properties. OBJECTIVE: In this study, we hypothesized that atorvastatin could prevent the neurons lost in the hippocampal dentate gyrus region after transient global Ischemia/Reperfusion (I/R) through its anti- oxidant and anti-apoptotic activities. METHOD: Twenty-four male Wistar rats, 12-13 weeks old and weighing 250-300 g, were divided randomly into four groups: control, I/R, vehicle (I/R treated with NaCl) and experiment (I/R treated with atorvastatin, 10 mg/kg); rats were sacrificed 96 hours after I/R. Quantitative expression of genes (caspase 8, p53, bax, bcl2, cytochrome c) was studied. The MDA level, SOD, CAT, and GPx activities were measured with biochemical tests. To detect apoptotic cells, TUNEL and Nissl staining were performed. Mitochondria were prepared from the hippocampus rats and used for the quantification of mitochondrial ROS, ATP level, GSH content, membrane potential, cytochrome c release, and determination of mitochondrial swelling. RESULTS: Atorvastatin attenuated the overexpression of bax, cytochrome C, p53, and caspase8 mRNAs and induced expression of bcl-2 mRNA (P<0.001). Atorvastatin treatment increased anti-oxidant enzyme levels (P<0.01). Treatment with atorvastatin reduced the number of TUNEL-positive cells. It could decrease the cytochrome c release (P<0.01), inhibit the decrease of MMP (P<0.001) and increase the ATP level (P<0.001) in hippocampal mitochondria compared with the I/R group. CONCLUSION: Atorvastatin treatment in I/R rats decreases oxidative stress, production of ROS, apoptosis rate in neuronal cells, and improves the mitochondrial function. Hence, atorvastatin has a proper neuronal protective effect against the I/R injury in the brain.
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Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Atorvastatina/farmacologia , Morte Celular/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Animais , Isquemia Encefálica/tratamento farmacológico , Giro Denteado/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Masculino , Mitocôndrias/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Neurônios , Estresse Oxidativo , Ratos , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
It is of great importance to find an effective approach that not only eliminates gastric cancer cells but also do exhibits significant side effect to normal cells. Some studies have shown the effectiveness of hypericin against cancer cells. In this study, we evaluated the anti-cancer effect of Hypericin in the treatment of gastric cancer. In this study, the AGS cell line was exposed to different concentrations of hypericin for 24 and 48 h. Evaluation of cell death was done by MTT assay. The rate of apoptosis was measured by flow cytometry assay using Annexin V/ Propidium Iodide. The expression rate of Bcl2, p53 and Bax genes was evaluated by Real-time PCR test, and immunocytochemistry (ICC) analysis and western blotting was used for further evaluation of p53. MTT assay test showed that hyepricin induces 50% cell death in the concentration of 1 (µg/mL) and 0.5 (µg/mL) at 24 h and 48 h post-treatment, respectively, however no similar effect seen on fibroblast cells. Annexin/PI test revealed that cell apoptosis after exposure to hypericin for 24 h was 74%. Real-time PCR showed that expression level of Bax, p53 and Bax genes increases and Bcl2 gene decreases in AGS cell lines after treatment by hypericin. ICC analysis and western blotting for p53 confirmed these data. The results of this study indicated that hypericin has the potential to be introduced as an effective treatment for gastric cancer. Therefore, it seems that this substance has potential to be utilized as anti-cancer drug.
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The prefrontal cortex is the largest lobe of the brain and is consequently involved in stroke. There is no comprehensive practical pharmacological strategy for ameliorating prefrontal cortex injury induced by cerebral ischemia. Therefore, we studied the neuroprotective properties of verapamil (Ver) on mitochondrial dysfunction and morphological features of apoptosis in transient global ischemia/reperfusion (I/R). Ninety-six Wistar rats were allocated into four groups: control, I/R, I/R+Ver (10 mg/kg twice 1 hour prior to ischemia and 1 hour after reperfusion phase), and I/R+NaCl (vehicle). Animals were sacrificed, and mitochondrial dysfunction parameters (i.e., mitochondrial swelling, mitochondrial membrane potential, ATP concentration, ROS production, and cytochrome c release), antioxidant defense (i.e., superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, and caspase-3 activation), and morphological features of apoptosis were determined. The results showed that mitochondrial damage, impairment of antioxidant defense system, and apoptosis were significantly more prevalent in the I/R group in comparison with the other groups. Ver decreased mitochondrial damage by reducing oxidative stress, augmented the activity of antioxidant enzymes in the brain, and decreased apoptosis in the I/R neurons. The current study confirmed the role of oxidative stress and mitochondrial dysfunction in I/R progression and indicated the possible antioxidative mechanism of the neuroprotective activities of Ver.
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Apoptose , Ataque Isquêmico Transitório/patologia , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia , Verapamil/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Ataque Isquêmico Transitório/complicações , Masculino , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Dilatação Mitocondrial/efeitos dos fármacos , Degeneração Neural/complicações , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Traumatismo por Reperfusão/complicações , Verapamil/administração & dosagemRESUMO
BACKGROUND: Central nervous system tuberculoma is the most severe manifestation of extrapulmonary tuberculosis with high mortality. Cavernous sinus tuberculoma (CST) is a very rare central nervous system tuberculoma with few cases reported in the literature. CASE DESCRIPTION: A 57-year-old woman was admitted to our clinic with acute diplopia and headache limited to the right side. There was no specific medical history except for migraine, depression, and anxiety, all of which were controlled by oral medications. Physical examination revealed ptosis and mydriasis in the right eye, which indicated right third and sixth cranial nerve palsies. Pituitary magnetic resonance imaging showed a right parasellar lesion at the cavernous sinus wall and ophthalmic nerve. Laboratory examinations and brain computed tomography scan showed negative findings. Initial differential diagnosis included meningioma, sarcoidosis, tuberculoma, and lymphoma. However, results of further studies, including blood and cerebrospinal fluid cultures and Mycobacterium tuberculosis DNA assay, were negative. Biopsy of the cerebral lesion was performed through the subfrontal approach, and histopathologic study confirmed CST. She was treated with a standard antituberculous regimen. After 12 months of follow-up, no cerebral or clinical findings were seen. CONCLUSIONS: CST is a rare presentation of M. tuberculosis, and the diagnosis is a difficult challenge. However, accurate diagnosis and timely treatment of CST can result in complete cure.
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Doenças do Nervo Abducente/etiologia , Seio Cavernoso , Doenças do Nervo Oculomotor/etiologia , Tuberculoma Intracraniano/complicações , Tuberculoma Intracraniano/diagnóstico , Doenças do Nervo Abducente/diagnóstico , Doenças do Nervo Abducente/patologia , Doenças do Nervo Abducente/terapia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Doenças do Nervo Oculomotor/diagnóstico , Doenças do Nervo Oculomotor/patologia , Doenças do Nervo Oculomotor/terapia , Tuberculoma Intracraniano/patologia , Tuberculoma Intracraniano/terapiaRESUMO
BACKGROUND: Breast cancer is the major cause of death from cancer among women around the world. Given the drug resistance in the treatment of this disease, it is very important to identify new therapies and anticancer drugs. Many studies demonstrated that hypericin could induce apoptosis in different cancer cell lines; however, the underlying mechanism is not well understood yet. Therefore, this study aimed to evaluate the anticancer effect of hypericin in two breast cancer cell lines, one with wild type P53 and the other with mutant P53. METHODS: In this study, the MDA-MB-231 and MDA-MB-175-VII cell lines were treated with different concentrations of hypericin for 24 and 48 hours. The measurement of cell death was performed by MTT assay. The cell apoptosis rate was measured using annexin V/propidium iodide assay through flow cytometry. The level of expression in P21 and P53 genes was evaluated by real time PCR. Immunocytochemistry (ICC) analysis was performed for P21 (direct target for P53 protein) to confirm the results. RESULTS: The results showed that hypericin could have dose-dependent cytotoxic effects on the MDA-MB-231 and MDA-MB-175-VII cell lines, and its cytotoxicity is much higher in the latter cells. According to flow cytometry results, 86% of MDA-MB-175-VII cells underwent apoptosis with IC50 dose of hypericin for MDA-MB-231 cells after 24 hours. Moreover, after 24 hours of exposure to hypericin with MDA- MB-231 IC50 concentration, the expression of P53 and P21 genes upregulated in MDA-MB-175-VII much more than MDA-MB-231 when both cell lines were treated with 24 hours IC50 dose of MDA-MB-231. The ICC analysis on P21 confirmed that by treating both cell lines with MDA-MB-231 IC50 dose of hypericin for 24 hours, this protein is overexpressed much more in MDA-MB-175-VII cells. CONCLUSION: The results of this study demonstrated that hypericin's apoptotic and cytotoxic effects on cancer cells may be mediated via P53 overexpression, cell cycle arrest and the subsequent apoptosis. Therefore, it is of great importance to consider that hypericin would have better impact on cells or tumors with wild type P53.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Perileno/análogos & derivados , Proteína Supressora de Tumor p53/genética , Antracenos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Perileno/farmacologiaRESUMO
OBJECTIVE: Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary cerebral tumor. The median survival time is 15 months despite maximum treatment because the tumor is resistant to most therapeutic modalities. Several studies have indicated chemopreventive and chemotherapeutic activity of cyanidin-3-glucoside (C3G) as an anthocyanin component. We aimed to illustrate the cytotoxic and apoptogenic effects of C3G in the U87 cell line (human GBM cell line). METHODS: Cytotoxic activity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium assay after treatment with C3G at different concentrations in the U87 cell line. Cisplatin was used as a positive control for 24 and 48 hours. The percentage of apoptotic cells was determined using an Annexin V/propidium iodide assay, and the expression of bax, bcl2, and p53 genes was assessed using real-time polymerase chain reaction. RESULTS: Treatment of U87 cells with 40 µg/mL of C3G resulted in 32% apoptotic cells after 24 hours. To further confirm that C3G treatment induced apoptosis in U87 cells, RNA expression of bax, bcl2, and p53 genes was investigated after treatment. Real-time polymerase chain reaction indicated that the expression of bax and p53 increased, whereas the expression of bcl2 decreased. CONCLUSIONS: C3G had an apoptogenic effect in the GBM cell line. New information regarding the therapeutic effects of C3G in GBM could ultimately lead to the production of new drugs.
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Antocianinas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glucosídeos/farmacologia , Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
This study was aimed at evaluating the protective effect of coenzyme Q10 on L-arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1ß, and TNF-α, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-α and IL-1ß cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role.
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Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Pancreatite/tratamento farmacológico , Ubiquinona/análogos & derivados , Amilases/sangue , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Arginina , Citocinas/sangue , Lipase/sangue , Masculino , Estresse Oxidativo , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/enzimologia , Pancreatite/patologia , Ratos Sprague-Dawley , Ubiquinona/farmacologia , Ubiquinona/uso terapêuticoRESUMO
BACKGROUND: Histologically similar tumors may have different prognoses and responses to treatment. These differences are due to molecular differences. Hence, in this review, the biological interaction of breast cancer in several different areas is discussed. In addition, the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from a biological perspective and current global advances in these areas are addressed. OBJECTIVE: This review provides the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from the biological perspective and current global advances in these areas. METHODS: PubMed, Scopus, and Google Scholar were searched comprehensively with combinations of the following keywords: "breast cancer," "biological markers," and "clinical." The definition of breast cancer, diagnostic methods, biological markers, and available treatment approaches were extracted from the literature. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67 are the most well-known biological markers that have important roles in prognosis and response to therapeutic methods. Some studies showed the response of ER-positive and PR-negative tumors to anti-estrogenic treatment to be lower than ER-positive and PR-positive tumors. Patients with high expression of HER-2 and Ki-67 had a poor prognosis. In addition, recent investigations indicated the roles of new biomarkers, such as VEGF, IGF, P53 and P21, which are associated with many factors, such as age, race, and histological features. CONCLUSION: The objective of scientists, from establishing a relationship between cancer biology infrastructures with clinical manifestations, is to find new ways of prevention and progression inhibition and then possible introduction of less dangerous and better treatments to resolve this dilemma of human society.
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Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies showed that magnesium (Mg) has cytotoxic effects on malignant cell lines. However, the anti-cancer effects of Mg on MCF-7 breast cancer cells are uncertain. This study was aimed at the comparison of the cytotoxic effect of Mg salt (MgCl2) and cisplatin on MCF-7 cells and fibroblasts (as normal cells). After treatment with various concentrations of MgCl2, and cisplatin as a positive control for 24 and 48 hours (h), cytotoxicity activity was measured by MTT assay. In addition, apoptosis was determined by annexin V/propidium iide assay. Both cisplatin and the MgCl2 exhibited dose-dependent cytotoxic effects in the MCF-7 cell line, although the LD50 of the Mg was significantly higher when compared to cispaltin (40 µg/ml vs. 20 µg/ml). Regarding annexin V/propidium results, treatment of MCF-7 cells with LD50 concentrations of cisplatin and Mg showed 59% and 44% apoptosis at 24h, respectively. Finally, the results indicated that Mg has cytotoxic effects on MCF-7 cells, but less than cisplatin as a conventional chemotherapeutic agent. However, regarding the side effects of chemotherapy drugs, it seems that Mg can be considered as a supplement for the treatment of breast cancer.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Cloreto de Magnésio/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Humanos , Células MCF-7RESUMO
INTRODUCTION: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by mucocutaneous perioral pigmentation, gastrointestinal hamartomatous polyposis, and an increased risk of malignancy. Families with PJS may show a variable spectrum of manifestations in spite of their consecutive generations. A probable explanation is novel mutations in contributing genes. CASE PRESENTATION: This report describes 3 cases of a family. Two daughters presented the classic PJS, while their father only manifested mucocutaneous perioral pigmentation. The junior daughter was underwent 3 and the eldest daughter 2 laparotomies for intussusception. The patients were visited annually and their medical findings were recorded during a follow-up period of 14 years. They were periodically examined in our hospital and despite conveying diffuse polyposis from the esophagus throughout the rectum in these three cases, even a simple hyperplasia was not found in obtained specimens. CONCLUSIONS: The patients with diffuse PJS may be asymptomatic and without gastrointestinal or extragastrointestinal malignancies.
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Delayed wound healing process is one of the most important concerns in diabetes. Healing of wounds has four phases, namely, hemostasis, inflammation, proliferation, and remodeling. For a successful repair, all four factors must occur properly. Hence, we aimed to evaluate the healing effects of Hypericum perforatum (HP) on full-thickness diabetic skin wounds by using stereological methods. Forty-eight female diabetic rats were randomly divided into four groups (n = 12): gel base treated group, HP 5% gel treated group, HP 10% gel treated group, and the control group which received no treatment. A circular 1 cm(2) full-thickness wound was created on the animal's neck and wound area was measured every three days. After sacrificing the animals, skin samples were fixed and prepared for stereological evaluations. Based on the results, HP treated group showed faster wound closure rate in comparison with control and vehicle groups (P < 0.05). In addition, numerical density of fibroblasts, volume density of collagen bundles, and mean diameter and volume densities of the vessels in HP group were significantly higher than control and vehicle groups. The results of this study showed that HP has the ability to improve tissue regeneration by enhancing fibroblast proliferation, collagen bundle synthesis, and revascularization.
RESUMO
BACKGROUND: Nephrolithiasis is of the most prevalent urinary tract disease. It seems worthwhile to replace the conventional treatments with more beneficial and safer agents, particularly herbal medicines which are receiving an increasing interest nowadays. AIMS: In this study, we investigated the protective and curative effects of Achillea millefolium L. on ethylene glycol (EG)-induced nephrolithiasis in rats. MATERIALS AND METHODS: The extract of A. millefolium was prepared by soxhlet method. Forty male Wistar rats were randomly divided into five groups (N = 8) as follows. The negative control (group A) received tap drinking water. Rats in sham (positive control group B), curative (group C and D), and preventive (group E) groups all received 1% EG in drinking water according to the experimental protocol for 30 days. In the curative groups, dosages of 200 and 400 mg/kg body weight (BW) of A. millefolium extract were administered orally from day 15 to the end of the experiment, group C and D, respectively. Group E received 200 mg/kg A. millefolium extract from the 1(st) day throughout the experiment. Urinary oxalate and citrate concentrations were measured by spectrophotometer on the first and 30(th) days. On day 31, the kidneys were removed and examined histopathologically for counting the calcium oxalate (CaOx) deposits in 50 microscopic fields. RESULTS: In the curative and preventive groups, administration of A. millefolium extract showed significant reduction in urinary oxalate concentration (P < 0.05). Also, urinary citrate concentration was significantly increased in group C, D, and E. The CaOx deposits significantly decreased in group C to E compared with the group B. CONCLUSIONS: According to our results, A. millefolium extract had preventive and curative effects on EG-induced renal calculi.